Anti-HIV drugs Lopinavir and Ritonavir are no longer India’s drugs of choice against the novel coronavirus disease (COVID-19). Instead, a combination of hydroxychloroquine (HCQ), used for treatment of auto-immune disorders, and the antibitoic azithromycin has now been recommended for use in severe patients in new clinical management guidelines issued late on Tuesday night.

The earlier guidelines, dated March 17, which included use of Ritonavir-Lopinavir in high risk patients, now stand repealed.

The revised guidelines state: “No specific antivirals have been proven to be effective as per currently available data. However, based on the available information (uncontrolled clinical trials), the following drugs may be considered as an off-label indication in patients with severe disease and requiring ICU management.”

Earlier this month, India had also recommended use of HCQ as a prophylactic in medical workers managing coronavirus patients and caregivers at home, leading to a huge surge in demand. The drug regulator had then stepped in to put it on a schedule of the Drugs and Cosmetics Act, which requires stricter control of sales. The drug cannot be sold without prescription.India’s earlier drugs of choice had suffered a blow when 199-subject Chinese trial returned a negative.

Azithromycin is a commonly used antibiotic, while HCQ is used in treatment of autoimmune diseases such as rheumatoid arthritis. It is also used in treating malaria. The azithromycin-hydroxychloroquine combination is part of an upcoming multi-country trial anchored by the World Health Organization to examine the efficacy of various drug combinations against COVID-19.

It had found an advocate in US President Donald Trump, who had recently tweeted: “HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine. The FDA has moved mountains – Thank You! Hopefully they will BOTH (H works better with A, International Journal of Antimicrobial Agents)…..be put in use IMMEDIATELY. PEOPLE ARE DYING, MOVE FAST, and GOD BLESS EVERYONE!”

The tweet, however, caused outrage in the US, as the combination is yet to get regulatory approvals in that country. The US National Institute of Allergy and Infectious Diseases’ director, Dr Anthony Fauci, called evidence of the efficacy of the combination “anecdotal”.

In a small study published in the ‘International Journal of Antimicrobial Agents’ on March 17, French scientists reported: “Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.”

In other words, the combination did reduce the viral load but the size of the study is too small for the conclusion to be treated as definitive.

India’s earlier drugs of choice had suffered a blow when 199-subject Chinese trial returned a negative. At 22.1 per cent, the mortality reported in the trial was substantially higher than the 11 per cent to 14.5 per cent mortality reported in initial studies of patients hospitalised with COVID-19.

The overall documented mortality of COVID-19, as given out by the WHO is 3.4 per cent. India had announced its decision to be part of the WHO global trials, which are also looking at these two drugs